Inactive GSK3b is disturbed in the spinal cord during experimental autoimmune encephalomyelitis, but rescued by stem cell therapy

Azita Parvaneh Tafreshi, Natalie Lisa Payne, Guizhi Sun, Aude Sylvain, Keith Estment Schulze, Claude C A Bernard

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Glycogen synthase kinase 3beta (GSK3beta) is known to control neuroinflammation, however the status of GSK3beta in multiple sclerosis, the most common inflammatory demyelinating disease of the CNS, and its animal model EAE, is unknown. In this study, we investigated the expression of phosphorylated GSK3beta, the inactive form of GSK3beta, in the spinal cords of EAE mice. We demonstrate that while the expression of phosphorylated GSK3beta was present in radial astrocytes and neurons of the control mice that received only complete Freund s adjuvant, it was absent in radial astrocytes and significantly lower in neurons of EAE animals. The loss of phosphorylated GSK3beta in radial glia and neurons in EAE spinal cords was concurrent with radial glia migration and astrogliosis. This disturbance in the expression of inactive GSK3beta was recovered in neurons, but not in the radial glia, after treatment of EAE mice with adipose-derived mesenchymal stem cells capable of inducing a Th2 shift. Collectively, our results suggest a link between inactive GSK3beta and modulation of the immune responses during EAE. Thus, we propose that maintenance of GSK3beta in its inactive status may play a role in preserving the normal physiology of the spinal cord and amelioration of EAE following stem cell therapy.
Original languageEnglish
Pages (from-to)498 - 505
Number of pages8
JournalNeuroscience
Volume277
DOIs
Publication statusPublished - 2014

Cite this

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title = "Inactive GSK3b is disturbed in the spinal cord during experimental autoimmune encephalomyelitis, but rescued by stem cell therapy",
abstract = "Glycogen synthase kinase 3beta (GSK3beta) is known to control neuroinflammation, however the status of GSK3beta in multiple sclerosis, the most common inflammatory demyelinating disease of the CNS, and its animal model EAE, is unknown. In this study, we investigated the expression of phosphorylated GSK3beta, the inactive form of GSK3beta, in the spinal cords of EAE mice. We demonstrate that while the expression of phosphorylated GSK3beta was present in radial astrocytes and neurons of the control mice that received only complete Freund s adjuvant, it was absent in radial astrocytes and significantly lower in neurons of EAE animals. The loss of phosphorylated GSK3beta in radial glia and neurons in EAE spinal cords was concurrent with radial glia migration and astrogliosis. This disturbance in the expression of inactive GSK3beta was recovered in neurons, but not in the radial glia, after treatment of EAE mice with adipose-derived mesenchymal stem cells capable of inducing a Th2 shift. Collectively, our results suggest a link between inactive GSK3beta and modulation of the immune responses during EAE. Thus, we propose that maintenance of GSK3beta in its inactive status may play a role in preserving the normal physiology of the spinal cord and amelioration of EAE following stem cell therapy.",
author = "Tafreshi, {Azita Parvaneh} and Payne, {Natalie Lisa} and Guizhi Sun and Aude Sylvain and Schulze, {Keith Estment} and Bernard, {Claude C A}",
year = "2014",
doi = "10.1016/j.neuroscience.2014.07.013",
language = "English",
volume = "277",
pages = "498 -- 505",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier",

}

Inactive GSK3b is disturbed in the spinal cord during experimental autoimmune encephalomyelitis, but rescued by stem cell therapy. / Tafreshi, Azita Parvaneh; Payne, Natalie Lisa; Sun, Guizhi; Sylvain, Aude; Schulze, Keith Estment; Bernard, Claude C A.

In: Neuroscience, Vol. 277, 2014, p. 498 - 505.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Inactive GSK3b is disturbed in the spinal cord during experimental autoimmune encephalomyelitis, but rescued by stem cell therapy

AU - Tafreshi, Azita Parvaneh

AU - Payne, Natalie Lisa

AU - Sun, Guizhi

AU - Sylvain, Aude

AU - Schulze, Keith Estment

AU - Bernard, Claude C A

PY - 2014

Y1 - 2014

N2 - Glycogen synthase kinase 3beta (GSK3beta) is known to control neuroinflammation, however the status of GSK3beta in multiple sclerosis, the most common inflammatory demyelinating disease of the CNS, and its animal model EAE, is unknown. In this study, we investigated the expression of phosphorylated GSK3beta, the inactive form of GSK3beta, in the spinal cords of EAE mice. We demonstrate that while the expression of phosphorylated GSK3beta was present in radial astrocytes and neurons of the control mice that received only complete Freund s adjuvant, it was absent in radial astrocytes and significantly lower in neurons of EAE animals. The loss of phosphorylated GSK3beta in radial glia and neurons in EAE spinal cords was concurrent with radial glia migration and astrogliosis. This disturbance in the expression of inactive GSK3beta was recovered in neurons, but not in the radial glia, after treatment of EAE mice with adipose-derived mesenchymal stem cells capable of inducing a Th2 shift. Collectively, our results suggest a link between inactive GSK3beta and modulation of the immune responses during EAE. Thus, we propose that maintenance of GSK3beta in its inactive status may play a role in preserving the normal physiology of the spinal cord and amelioration of EAE following stem cell therapy.

AB - Glycogen synthase kinase 3beta (GSK3beta) is known to control neuroinflammation, however the status of GSK3beta in multiple sclerosis, the most common inflammatory demyelinating disease of the CNS, and its animal model EAE, is unknown. In this study, we investigated the expression of phosphorylated GSK3beta, the inactive form of GSK3beta, in the spinal cords of EAE mice. We demonstrate that while the expression of phosphorylated GSK3beta was present in radial astrocytes and neurons of the control mice that received only complete Freund s adjuvant, it was absent in radial astrocytes and significantly lower in neurons of EAE animals. The loss of phosphorylated GSK3beta in radial glia and neurons in EAE spinal cords was concurrent with radial glia migration and astrogliosis. This disturbance in the expression of inactive GSK3beta was recovered in neurons, but not in the radial glia, after treatment of EAE mice with adipose-derived mesenchymal stem cells capable of inducing a Th2 shift. Collectively, our results suggest a link between inactive GSK3beta and modulation of the immune responses during EAE. Thus, we propose that maintenance of GSK3beta in its inactive status may play a role in preserving the normal physiology of the spinal cord and amelioration of EAE following stem cell therapy.

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